PMID: 2112276May 1, 1990Paper

Carbamazepine metabolism in humans: effect of concurrent anticonvulsant therapy

Therapeutic Drug Monitoring
R E RamsayP Wong

Abstract

Free and total carbamazepine (CBZ) and carbamazepine-epoxide (CBZ-EP) plasma levels were obtained on 113 patients with epilepsy (18-61 years old) controlled on either monotherapy or coadministration with either phenobarbital (PB), phenytoin (PHT), valproic acid (VPA), or all three. A subset of patients were administered tetradeuterium labeled CBZ to evaluate the effects of autoinduction and coadministration of VPA on the kinetics of CBZ and its metabolite CBZ-EP. Polytherapy had variable effect on free and total CBZ plasma levels compared to monotherapy. Coadministered PHT (co-PHT), or all three anticonvulsants together (PHT, PB, and VPA: co-AEDs) decreased free and total CBZ plasma levels. No change was noted for coadministered VPA (co-VPA). Compared to monotherapy the free and total CBZ-EP levels increased with co-VPA, less with coadministered PB (co-PB), and no change with co-PHT or co-AEDs. Protein binding of CBZ and CBZ-EP was not affected by any antiepileptic drugs studied. The free and total CBZ-EP/CBZ ratio was tripled with co-VPA or co-AED's, and doubled with co-PHT or co-PB. Isotope labeling did not demonstrate any differences in half-life (t1/2), plasma clearance (Cl), or volume of distribution (Vd). Compared to naiv...Continue Reading

Citations

Jun 1, 1994·Annals of Neurology·E L SoK W Weatherford
Mar 1, 1994·Journal of Clinical Pharmacology·S M TangeP E Senécal
Jan 1, 1991·European Journal of Clinical Pharmacology·P PetitR Pouget
Jan 1, 1996·Epilepsia·B F Bourgeois
Sep 24, 2010·NMR in Biomedicine·Mathilde H LercheJan H Ardenkjaer-Larsen
Dec 7, 2007·Journal of Separation Science·Lucie BudakovaJan Fischer
Dec 16, 1998·Therapeutic Drug Monitoring·J M Potter, A Donnelly
Apr 1, 1997·Therapeutic Drug Monitoring·M F Delgado IribarnegarayA Domínguez-Gil
Jul 21, 2011·Asian Pacific Journal of Tropical Medicine·Hemantkumar Somabhai Chaudhari, Prati Pal Singh
Oct 1, 1993·The Annals of Pharmacotherapy·D M CollinsM E Pitterle

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